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Long-term effects of early postnatal stress on Sertoli cells functions

View ORCID ProfileKristina M. Thumfart, Samuel Lazzeri, Francesca Manuella, Isabelle M. Mansuy
doi: https://doi.org/10.1101/2022.07.27.501498
Kristina M. Thumfart
1Laboratory of Neuroepigenetics, Institute for Neuroscience, Department of Health Sciences and Technology, ETH Zurich, Zurich, Switzerland
2Laboratory of Neuroepigenetics, Brain Research Institute, Medical Faculty of the University of Zurich, Zurich, Switzerland
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  • ORCID record for Kristina M. Thumfart
Samuel Lazzeri
1Laboratory of Neuroepigenetics, Institute for Neuroscience, Department of Health Sciences and Technology, ETH Zurich, Zurich, Switzerland
2Laboratory of Neuroepigenetics, Brain Research Institute, Medical Faculty of the University of Zurich, Zurich, Switzerland
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Francesca Manuella
1Laboratory of Neuroepigenetics, Institute for Neuroscience, Department of Health Sciences and Technology, ETH Zurich, Zurich, Switzerland
2Laboratory of Neuroepigenetics, Brain Research Institute, Medical Faculty of the University of Zurich, Zurich, Switzerland
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Isabelle M. Mansuy
1Laboratory of Neuroepigenetics, Institute for Neuroscience, Department of Health Sciences and Technology, ETH Zurich, Zurich, Switzerland
2Laboratory of Neuroepigenetics, Brain Research Institute, Medical Faculty of the University of Zurich, Zurich, Switzerland
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  • For correspondence: imansuy@ethz.ch
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Abstract

Sertoli cells are somatic cells in testes essential for spermatogenesis, as they support the development, maturation, and differentiation of germ cells. Sertoli cells are metabolically highly active and physiologically regulated by external signals, particularly factors in the blood stream. In disease conditions, circulating pathological signals may affect Sertoli cells and consequentially, alter germ cells and fertility. While the effects of stress on reproductive cells have been well studied, how Sertoli cells respond to stress remains poorly characterized. Therefore, we used a mouse model of early postnatal stress to assess the effects of stress on Sertoli cells. We developed an improved enrichment strategy based on intracellular stainings and obtained enriched preparations of adult Sertoli cells from exposed males. We show that adult Sertoli cells have impaired electron transport chain (ETC) pathways and that several components of ETC complexes I, III, and IV are persistently affected. We identify the circulation as a potential mediator of the effects of stress, since treatment of primary Sertoli cells with serum from stressed males induces similar ETC alterations. These results newly highlight Sertoli cells as cellular targets of early life stress, and suggest that they may contribute to the negative effects of stress on fertility.

Highlights

  • We present an improved method to obtain enriched preparations of Sertoli cells from adult mouse testis for molecular analyses

  • Sertoli cells from adult males exposed to stress during early postnatal life have altered electron transport chain (ETC) expression, suggesting persistent effects of early life stress on Sertoli cells physiology

  • Serum from adult males exposed to early postnatal stress reproduces ETC gene dysregulation in cultured Sertoli cells.

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Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Posted July 27, 2022.
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Long-term effects of early postnatal stress on Sertoli cells functions
Kristina M. Thumfart, Samuel Lazzeri, Francesca Manuella, Isabelle M. Mansuy
bioRxiv 2022.07.27.501498; doi: https://doi.org/10.1101/2022.07.27.501498
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Long-term effects of early postnatal stress on Sertoli cells functions
Kristina M. Thumfart, Samuel Lazzeri, Francesca Manuella, Isabelle M. Mansuy
bioRxiv 2022.07.27.501498; doi: https://doi.org/10.1101/2022.07.27.501498

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